Structural Linkage between Ligand Discrimination and Receptor Activation by Type I Interferons
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Thomas, Christoph | |
dc.contributor.author | Moraga, Ignacio | |
dc.contributor.author | Levin, Doron | |
dc.contributor.author | Krutzik, Peter O. | |
dc.contributor.author | Podoplelova, Yulia | |
dc.contributor.author | Trejo, Angelica | |
dc.contributor.author | Lee, Choongho | |
dc.contributor.author | Yarden, Ganit | |
dc.contributor.author | Vleck, Susan E. | |
dc.contributor.author | Glenn, Jeffrey S. | |
dc.contributor.author | Nolan, Garry P. | |
dc.contributor.author | Piehler, Jacob | |
dc.contributor.author | Schreiber, Gideon | |
dc.contributor.author | Garcia, K. Christopher | |
dc.date.accessioned | 2021-12-23T16:18:01Z | - |
dc.date.available | 2021-12-23T16:18:01Z | - |
dc.date.issued | 2011 | |
dc.identifier.issn | 00928674 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/12498 | - |
dc.description.abstract | Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFN alpha 2 and IFN omega reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand ``anchor points'' interspersed among ligand-specific interactions that ``tune'' the relative IFN-binding affinities, in an apparent extracellular ``ligand proofreading'' mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns. | |
dc.description.sponsorship | International Human Frontier Science Program OrganizationHuman Frontier Science Program; European CommunityEuropean Commission [223608]; [NIH-RO1-AI51321]; [NIH-RO1-AI087917]; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI087917, R37AI051321, R01AI051321] Funding Source: NIH RePORTER; We thank Natalia Goriatcheva for expert technical assistance, the staff at SSRL and ALS for their assistance, and David Canner for preparing the Proteopedia pages. K. C. G. is an Investigator of the Howard Hughes Medical Institute. This work was also supported by NIH-RO1-AI51321 (K. C. G.) and NIH-RO1-AI087917 (J.S.G.), C. T. is supported by a long-term postdoctoral fellowship of the International Human Frontier Science Program Organization. G. S. and J.P. are supported by the European Community's FP7/2007-2013 under GA no. 223608 (IFNaction). | |
dc.language.iso | en | |
dc.publisher | CELL PRESS | |
dc.relation.ispartof | CELL | |
dc.subject | AFFINITY | |
dc.subject | ALPHA | |
dc.subject | BINDING-SITE | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | Cell Biology | |
dc.subject | COMPLEX REVEALS | |
dc.subject | CRYSTAL-STRUCTURE | |
dc.subject | GAMMA | |
dc.subject | IFN-ALPHA-2 | |
dc.subject | IFNAR1 | |
dc.subject | MUTANT | |
dc.subject | MUTATIONAL ANALYSIS | |
dc.title | Structural Linkage between Ligand Discrimination and Receptor Activation by Type I Interferons | |
dc.type | journal article | |
dc.identifier.doi | 10.1016/j.cell.2011.06.048 | |
dc.identifier.isi | ISI:000294043600016 | |
dc.description.volume | 146 | |
dc.description.issue | 4 | |
dc.description.startpage | 621 | |
dc.description.endpage | 632 | |
dc.contributor.orcid | 0000-0002-8862-9043 | |
dc.contributor.orcid | 0000-0001-7441-1089 | |
dc.contributor.orcid | 0000-0001-9909-0701 | |
dc.contributor.researcherid | AAZ-9876-2020 | |
dc.contributor.researcherid | AAE-7903-2019 | |
dc.identifier.eissn | 10974172 | |
dc.publisher.place | 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA | |
dcterms.isPartOf.abbreviation | Cell | |
dcterms.oaStatus | Bronze, Green Accepted | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PiJa938 | - |
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geprüft am 13.05.2024